Overview

Dosing for RYBREVANT® + LAZCLUZE®

Premedications1

Administer antihistamine, antipyretic, and glucocorticoids*:

15 to 60 minutes prior to each infusion according to the recommended premedications in the table below.

*Glucocorticoid administration is required for week 1, days -2, -1, 1, and 2 doses only and upon reinitiation after prolonged dose interruptions, then as necessary for subsequent infusions.

See recommended premedications

Decreasing infusion times2†

In the MARIPOSA trial, infusion times decreased over time.†

†Total infusion time is approximately 4 to 6 hours for day 1 and 6 to 8 hours for day 2.1

See infusion details

Proactive medications1

To help reduce the risk of select ARs

  • Dermatologic AR prophylaxis:
    • Oral/topical antibiotics and ceramide-based moisturizer​
    • Advise patients to limit direct sun exposure‡
  • VTE concomitant medications: Anticoagulant prophylaxis for the first 4 months of treatment

‡During and for 2 months after treatment.

See Proactive Therapy Management

AR, adverse reaction; VTE, venous thromboembolism.

RYBREVANT FASPRO™ dosing and administration guide thumbnail

RYBREVANT® Administration & Management Guide

Download a guide with comprehensive dosing, administration, and proactive therapy management details for RYBREVANT®-based regimens.

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Dosing Schedule

Recommended dosing schedule for RYBREVANT® + LAZCLUZE® or RYBREVANT® monotherapy (Q2W)1,3

Recommended dosing schedule for RYBREVANT® and LAZCLUZE® for Q2W. For RYBREVANT®, the dose is 1,050 mg for patients less than 80 kg and 1,400 mg for those 80 kg or more. Week 1 is the first dose, which is split into an infusion between day 1 and day 2. For the next 4 doses (Weeks 2-5), there is 1 infusion each week. Week 6 has no dose. From Week 7+, maintenance involves 1 infusion Q2W until disease progression or unacceptable toxicity. LAZCLUZE® is administered as 240 mg orally once daily throughout the schedule.Recommended dosing schedule for RYBREVANT® and LAZCLUZE® for Q2W. For RYBREVANT®, the dose is 1,050 mg for patients less than 80 kg and 1,400 mg for those 80 kg or more. Week 1 is the first dose, which is split into an infusion between day 1 and day 2. For the next 4 doses (Weeks 2-5), there is 1 infusion each week. Week 6 has no dose. From Week 7+, maintenance involves 1 infusion Q2W until disease progression or unacceptable toxicity. LAZCLUZE® is administered as 240 mg orally once daily throughout the schedule.

*Dose adjustments not required for subsequent body weight changes.

RYBREVANT®

The recommended dosage is based on baseline body weight and can be administered as an intravenous infusion after dilution.1

With LAZCLUZE®

Administer RYBREVANT® any time after LAZCLUZE® when given on the same day.1

Refer to the full Prescribing Information for LAZCLUZE® for recommended LAZCLUZE® dosing information.

Patients currently receiving RYBREVANT® may switch to RYBREVANT FASPRO™

If switching from RYBREVANT® Q2W dosing to RYBREVANT FASPRO™ Q4W or Q2W, switch patients at their next scheduled dose on or after week 5.1

See Proactive Therapy Management to help reduce the risk of key ARs

Learn more

In the MARIPOSA trial, infusion times decreased over time with RYBREVANT®2

MARIPOSA clinical trial median infusion times by hours graphMARIPOSA clinical trial median infusion times by hours graph

Total infusion time is approximately 4 to 6 hours for day 1 and 6 to 8 hours for day 2. Subsequent infusion time is approximately 2 hours.1

*Data reflect results from 2-week dosing in the MARIPOSA trial.1

Q2W, once every 2 weeks; Q4W, once every 4 weeks.

Premedications

Premedications for RYBREVANT®1

IRR management

MedicationDoseAdministrationFrequency
GlucocorticoidDexamethasone (8 mg) or equivalent
Oral48 hours, 24 hours, and 60 minutes prior
Week 1, day -2 (twice daily), day -1 (twice daily), day 1 (one dose)
GlucocorticoidDexamethasone (20 mg) or equivalent
IV45–60 minutes prior
Week 1, day 1 (one dose)
GlucocorticoidDexamethasone (10 mg)
or equivalent
IV45–60 minutes prior
Week 1, day 2 (one dose)
AntihistamineDiphenhydramine (25–50 mg) or equivalent
IV15–30 minutes prior
OR
Oral30–60 minutes prior
All doses
AntipyreticAcetaminophen (650–1,000 mg)
IV15–30 minutes prior
OR
Oral30–60 minutes prior
All doses
Glucocorticoid (optional)Dexamethasone (10 mg)
or equivalent
IV45–60 minutes prior
Optional for subsequent doses
MedicationGlucocorticoid
DoseDexamethasone (8 mg) or equivalent
Administration
Oral
48 hours, 24 hours, and 60 minutes prior
FrequencyWeek 1, day -2 (twice daily), day -1 (twice daily), day 1 (one dose)
MedicationGlucocorticoid
DoseDexamethasone (20 mg) or equivalent
Administration
IV
45–60 minutes prior
FrequencyWeek 1, day 1 (one dose)
MedicationGlucocorticoid
DoseDexamethasone (10 mg)
or equivalent
Administration
IV
45–60 minutes prior
FrequencyWeek 1, day 2 (one dose)
MedicationAntihistamine
DoseDiphenhydramine (25–50 mg) or equivalent
Administration
IV
15–30 minutes prior
OR
Oral
30–60 minutes prior
FrequencyAll doses
MedicationAntipyretic
DoseAcetaminophen (650–1,000 mg)
Administration
IV
15–30 minutes prior
OR
Oral
30–60 minutes prior
FrequencyAll doses
MedicationGlucocorticoid (optional)
DoseDexamethasone (10 mg)
or equivalent
Administration
IV
45–60 minutes prior
FrequencyOptional for subsequent doses
  • Interrupt infusion if IRR is suspected. Reduce the infusion rate or permanently discontinue RYBREVANT® based on severity
  • If an anaphylactic reaction occurs, permanently discontinue RYBREVANT®
See additional strategies for IRR prophylaxis

Prophylactic and concomitant medications1

Dermatologic AR prophylaxis

Prophylactic measures (eg, use of oral/topical antibiotics) are recommended to reduce the risk of dermatologic ARs. When initiating treatment with RYBREVANT®, ceramide-based moisturizer is recommended.

See additional strategies for dermatologic AR prophylaxis

VTE concomitant medications

When initiating treatment with RYBREVANT® in combination with LAZCLUZE®, implement anticoagulant prophylaxis to reduce the risk of VTE events for the first 4 months of treatment.

  • The use of vitamin K antagonists is not recommended
  • If there are no signs or symptoms of VTE during the first 4 months of treatment, consider discontinuation of anticoagulant prophylaxis at the discretion of the healthcare provider
See additional information on VTE prophylaxis

Refer to the full Prescribing Information for LAZCLUZE® for information about concomitant medications.

IRR, infusion-related reaction; IV, intravenous.

Preparation

Preparation1,4

Dilute and prepare RYBREVANT® for IV infusion before administration

STEP

1

During preparation and prior to administration, check the vial labels to ensure that the drug being prepared and administered is RYBREVANT® and not subcutaneous RYBREVANT FASPRO™

Check that the RYBREVANT® solution is colorless to pale yellow. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use if discoloration or visible particles are present

STEP

2

Determine the dose required of RYBREVANT® based on patient’s baseline weight

  • Each vial of RYBREVANT® contains 350 mg of amivantamab-vmjw

STEP

3

Withdraw and then discard a volume of either 5% dextrose injection or 0.9% sodium chloride injection from the 250 mL infusion bag equal to the volume of RYBREVANT® to be added (ie, discard 7 mL diluent from the infusion bag for each RYBREVANT® vial)

  • Only use infusion bags made of PVC, PP, PE, or PP+PE

STEP

4

Withdraw 7 mL of RYBREVANT® from each vial and add it to the infusion bag. The final volume in the infusion bag should be 250 mL

  • Discard any unused portion left in the vial

STEP

5

Gently invert the bag to mix the solution. Do not shake

STEP

6

Diluted solutions should be administered within 10 hours (including infusion time) at room temperature

PE, polyethylene; PP, polypropylene; PVC, polyvinyl chloride.

Administration

Administering RYBREVANT® infusions1

Administer premedications before each RYBREVANT® dose as recommended to reduce the risk of IRRs.

  • Administer the diluted solution by IV infusion using an infusion set fitted with a flow regulator and with an in-line, sterile, non-pyrogenic, low protein-binding PES filter (pore size 0.2 micrometer)
  • Administration sets must be made of PU, PBD, PVC, PP, or PE
  • The administration set with filter must be primed with either 5% dextrose injection or 0.9% sodium chloride injection prior to the initiation of each RYBREVANT® infusion
  • Do not infuse RYBREVANT® concomitantly in the same IV line with other agents

Administering RYBREVANT® + LAZCLUZE® or RYBREVANT® as a single agent1

  • Administer RYBREVANT® as a single agent infusion every 2 weeks intravenously until disease progression or unacceptable toxicity according to the infusion rates
  • Administer RYBREVANT® via a peripheral line on week 1 and week 2 to reduce the risk of IRRs during initial treatment
  • RYBREVANT® may be administered via a central line for subsequent weeks
  • For the initial infusion, prepare RYBREVANT® as close to administration time as possible to allow for the possibility of extended infusion time in the event of an IRR

When given in combination with LAZCLUZE®, administer RYBREVANT® any time after LAZCLUZE® when given on the same day

Administering LAZCLUZE®3

Administer LAZCLUZE® 240 mg orally once daily

  • Swallow LAZCLUZE® tablets whole (with or without food). Do not crush, split, or chew
  • If a patient misses a dose of LAZCLUZE® within 12 hours, instruct the patient to take the missed dose. If more than 12 hours have passed since the dose was to be given, instruct the patient to take the next dose at its scheduled time
  • If vomiting occurs any time after taking LAZCLUZE®, instruct the patient to take the next dose at its next regularly scheduled time

Drug interactions with LAZCLUZE®3

Avoid concomitant use of LAZCLUZE® with strong and moderate CYP3A4 inducers. Consider an alternate concomitant medication with no potential to induce CYP3A4.

Monitor for adverse reactions associated with a CYP3A4 or BCRP substrate where minimal concentration changes may lead to serious adverse reactions, as recommended in the approved product labeling for the CYP3A4 or BCRP substrate.

Please read the full Prescribing Information for LAZCLUZE® for information regarding dosing and drug interactions.

BCRP, breast cancer resistance protein; CYP3A4, cytochrome P450 3A4; PBD, polybutadiene; PES, polyethersulfone; PU, polyurethane.

Body weight <80 kg
WeekDose (per 250 mL bag)Initial infusion rateSubsequent infusion rate*
Week 1 (split dose infusion)
Week 1, day 1350 mg50 mL/hr75 mL/hr
Week 1, day 2700 mg50 mL/hr75 mL/hr
Week 21,050 mg85 mL/hr
Week 31,050 mg125 mL/hr
Week 41,050 mg125 mL/hr
Week 51,050 mg125 mL/hr
Week 6No dose
Week 7 and every 2 weeks thereafter1,050 mg125 mL/hr
Body weight ≥80 kg
WeekDose (per 250 mL bag)Initial infusion rateSubsequent infusion rate*
Week 1 (split dose infusion)
Week 1, day 1350 mg50 mL/hr75 mL/hr
Week 1, day 21,050 mg35 mL/hr50 mL/hr
Week 21,400 mg65 mL/hr
Week 31,400 mg85 mL/hr
Week 41,400 mg125 mL/hr
Week 51,400 mg125 mL/hr
Week 6No dose
Week 7 and every 2 weeks thereafter1,400 mg125 mL/hr

*In the absence of IRRs, increase the initial infusion rate to the subsequent infusion rate after 2 hours based on patient tolerance. Total infusion time is approximately 4 to 6 hours for day 1 and 6 to 8 hours for day 2. Subsequent infusion time is approximately 2 hours.

References:

  1. RYBREVANT® [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.
  2. Data on file. Janssen Biotech, Inc.
  3. LAZCLUZE® [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.
  4. RYBREVANT FASPRO™ [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.